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EMF Effects on Microglia – Affects key proteins involved in neurodegenerative diseases

 

Molecular mechanisms of microglia- and astrocyte-driven neurorestoration triggered by application of electromagnetic fields

The study “Molecular Mechanisms of Microglia- and Astrocyte-driven Neurorestoration Triggered by Application of Electromagnetic Fields” by Jasmina Isaković, Dunja Gorup, and Dinko Mitrečić primarily focuses on the beneficial aspects of electromagnetic fields (EMFs) in promoting neurorestoration through the activation of microglia and astrocytes. However, understanding the mechanisms by which EMFs can positively affect neural tissue also provides insights into potential health risks associated with EMF exposure.

Potential Health Risks Highlighted by the Study

  1. Activation of Cellular Mechanisms:
    • HSPs and Stress Response: The study highlights the role of heat shock proteins (HSPs) in neurorestoration. HSPs are part of the cellular stress response, and their upregulation can indicate cellular stress. Chronic activation of stress pathways might lead to cellular damage or dysfunction over time.
    • ATP and Energy Metabolism: The modulation of ATP levels by EMFs can affect cellular energy metabolism. While short-term effects might be beneficial, prolonged or excessive alterations in ATP production could disrupt cellular homeostasis and lead to metabolic disorders.
  2. Calcium Signaling:
    • The study discusses the role of calcium ions (Ca2+) in mediating the effects of EMFs on microglia and astrocytes. Calcium signaling is crucial for various cellular functions, but dysregulated calcium homeostasis can lead to neurotoxicity, apoptosis, and other adverse effects on neural cells.
  3. Hypoxia-Inducible Factor 1α (HIF1α):
    • EMFs influence the expression of HIF1α, which is involved in cellular responses to low oxygen levels (hypoxia). While HIF1α activation can promote neuroprotection, chronic or inappropriate activation might contribute to pathological conditions such as tumorigenesis and abnormal cell growth.

Broader Implications and Concerns

  1. Chronic Exposure:
    • The beneficial effects of EMFs are typically studied under controlled conditions and specific parameters. However, real-world exposure to EMFs is often chronic and varies in intensity and frequency. This raises concerns about the long-term health impacts of continuous exposure to EMFs, including potential neurodegenerative effects or increased risk of neurological disorders.
  2. Non-Thermal Effects:
    • The study suggests that non-thermal mechanisms, such as changes in protein expression and signaling pathways, play a significant role in EMF-induced neurorestoration. These same mechanisms could also underlie adverse health effects, emphasizing the need to consider non-thermal biological effects in safety guidelines.
  3. Population Vulnerability:
    • Certain populations, such as children, pregnant women, and individuals with pre-existing health conditions, might be more vulnerable to EMF exposure. The activation of cellular stress responses and alterations in calcium signaling in these groups could lead to unintended health consequences.

Conclusion

While the study by Isaković, Gorup, and Mitrečić provides valuable insights into the therapeutic potentials of EMFs, it also highlights the complexity of EMF interactions with biological systems. The same mechanisms that can drive neurorestoration might also pose health risks, particularly with chronic exposure and in vulnerable populations. This underscores the importance of a balanced approach to EMF research, regulation, and public health policies, ensuring that the benefits of EMF applications are maximized while minimizing potential risks. Further research is needed to fully understand the long-term health impacts of EMFs and to develop comprehensive safety guidelines that protect the public from potential adverse effects.

 

EMF Effects on Microglia

Title: Mobile phone electromagnetic radiation affects Amyloid Precursor Protein and α-synuclein metabolism in SH-SY5Y cells

Authors: Aikaterina L. Stefi, Lukas H. Margaritis, Aikaterini S. Skouroliakou, Dido Vassilacopoulou

Published in: Pathophysiology, Volume 26, Issues 3–4, September–December 2019, Pages 203-212

DOI: 10.1016/j.pathophys.2019.02.004

Abstract

In this study, the effects of low-level GSM-emitted electromagnetic fields (EMF) on Amyloid Precursor Protein (APP) and alpha-synuclein (α-syn) in human neuroblastoma cells were investigated. The results indicated alterations in APP processing and cellular topology following EMF exposure (ℇ = 10.51 V/m, SAR = 0.23 W/kg, exposure time: 3 times, for 10 min, over 2 days). Changes in monomeric α-syn accumulation and multimerization, as well as induction of oxidative stress and cell death, were documented. These findings suggest potential links between EMF exposure and the molecular mechanisms involved in Alzheimer’s and Parkinson’s diseases.

Methods

Cell Culture:

  • SH-SY5Y Human Neuroblastoma Cell Line: The SH-SY5Y cells were chosen for their relevance as a model for studying neurodegenerative diseases. These cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM), a widely used nutrient mixture designed to support the growth and maintenance of various mammalian cells.
  • Supplementation: The DMEM was supplemented with 10% Fetal Bovine Serum (FBS), which provides necessary growth factors, hormones, and other nutrients. Antibiotics (penicillin/streptomycin) were added to prevent bacterial contamination.
  • Incubation Conditions: The cells were maintained in a humidified atmosphere with 5% CO2 at 37 °C, which is essential for maintaining the physiological pH and optimal growth conditions for the cells.

Exposure Conditions:

  • GSM 1800 MHz EMF: Cells were exposed to GSM (Global System for Mobile Communications) 1800 MHz EMF, which is commonly emitted by mobile phones. The specific field strength was 10.51 V/m.
  • SAR Value: The Specific Absorption Rate (SAR), a measure of the rate at which energy is absorbed by the body when exposed to an EMF, was set at 0.23 W/kg. This value ensures the exposure levels are within the range encountered during regular mobile phone usage.
  • Exposure Duration: Cells were exposed for 10 minutes per session, with three sessions conducted over two days. This intermittent exposure model was designed to simulate real-life mobile phone usage patterns.

Assays Used:

  • Immunostaining and Western Blot Analyses: These techniques were employed to detect APP fragments and α-syn. Immunostaining involves using antibodies to visualize specific proteins within cells, while Western blotting separates and identifies proteins based on their size and reactivity with specific antibodies.
  • Oxidative Stress Markers and Cytotoxicity Assays: These assays measured levels of oxidative stress and cell viability. Oxidative stress markers indicate the presence of reactive oxygen species (ROS) and other free radicals, while cytotoxicity assays assess cell death and overall cell health.

Results

Effect on APP Metabolism:

  • Altered APP Metabolism: EMF exposure resulted in changes in APP metabolism. There was a noticeable alteration in the processing and cellular localization of APP fragments, suggesting that EMF can disrupt normal cellular processes.
  • Shift in α-Syn Forms: A significant shift was observed from multimeric to monomeric forms of α-syn. This is particularly relevant for neurodegenerative processes, as the accumulation of monomeric α-syn is associated with the pathogenesis of diseases like Parkinson’s.

Oxidative Stress and Cytotoxicity:

  • Increased Oxidative Stress: EMF exposure induced oxidative stress, demonstrated by elevated levels of oxidative markers. This suggests that EMF can enhance the production of ROS, leading to cellular damage.
  • Increased Cell Death: There was a significant increase in cell death following EMF exposure, indicating cytotoxic effects. This further supports the hypothesis that EMF can compromise cell viability through oxidative damage.

Discussion

Neurodegenerative Diseases:

  • Alzheimer’s and Parkinson’s Diseases: Both AD and PD are characterized by the accumulation of abnormal protein aggregates—amyloid plaques in AD and Lewy bodies in PD. These aggregates disrupt neuronal function and lead to neurodegeneration.
  • Influence on Protein Metabolism: EMF exposure was found to influence the metabolism of APP and α-syn, two key proteins implicated in AD and PD. Alterations in the processing of these proteins can accelerate the formation of toxic aggregates, contributing to disease progression.

Implications for EMF Exposure:

  • Potential Health Risks: The study suggests that even low-level EMF exposure can alter protein metabolism associated with neurodegenerative diseases. This adds to the growing body of evidence that EMF exposure might contribute to the pathogenesis of conditions like AD and PD through oxidative stress and protein aggregation mechanisms.
  • Need for Further Research: The findings underscore the necessity for further research to elucidate the underlying mechanisms of EMF-induced changes in protein metabolism. Long-term studies on animal models and human subjects are crucial to fully understand the health risks associated with chronic EMF exposure.

Conclusions

The study concludes that GSM-emitted EMF can affect the metabolism of APP and α-syn in neuroblastoma cells, leading to oxidative stress and cell death. These alterations could potentially contribute to the development of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The findings highlight the need for updated guidelines and continued research into the non-thermal effects of EMF exposure, particularly as mobile phone use becomes more widespread.

Future Directions:

  • Mechanistic Studies: Further studies should focus on the cellular and molecular mechanisms underlying EMF-induced changes in APP and α-syn metabolism.
  • Long-Term Exposure Effects: Research on the long-term effects of chronic EMF exposure on brain health and neurodegeneration is essential.
  • Public Health Policies: There is an urgent need to review and update public health guidelines on EMF exposure to protect vulnerable populations and prevent neurodegenerative diseases.

In recent years, the proliferation of electromagnetic fields (EMFs) from mobile phones and other wireless devices has sparked growing concern about their potential health effects. A pivotal study published in Pathophysiology (Volume 26, Issues 3–4, September–December 2019) by Aikaterina L. Stefi et al. titled “Mobile phone electromagnetic radiation affects Amyloid Precursor Protein and α-synuclein metabolism in SH-SY5Y cells” explores the impact of EMF exposure on proteins linked to neurodegenerative diseases. This detailed report aims to examine the effects of EMFs on microglial cells, particularly focusing on the mechanisms of oxidative stress, protein metabolism, and potential implications for Alzheimer’s and Parkinson’s diseases.

Methods

Cell Culture:

  • The human neuroblastoma cell line SH-SY5Y was used for this study.
  • Cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) supplemented with 10% Fetal Bovine Serum and antibiotics.
  • The cultures were maintained in a humidified atmosphere with 5% CO2 at 37°C.

Exposure Conditions:

  • Cells were exposed to GSM 1800 MHz electromagnetic fields (EMF) at a field strength of 10.51 V/m and Specific Absorption Rate (SAR) of 0.23 W/kg.
  • The exposure schedule included 10-minute sessions repeated three times over two days.

Assays Used:

  • Immunostaining and Western blot analyses were performed to detect alterations in Amyloid Precursor Protein (APP) fragments and alpha-synuclein (α-syn).
  • Additional assays measured oxidative stress markers and cytotoxicity in the cells.

Results

Effect on APP Metabolism:

  • EMF exposure led to significant changes in APP metabolism, indicating altered processing and cellular localization of APP fragments.
  • Notably, there was a shift from multimeric to monomeric forms of α-syn, a critical change associated with neurodegenerative diseases.

Oxidative Stress and Cytotoxicity:

  • EMF exposure induced oxidative stress, evidenced by increased levels of oxidative markers.
  • There was also an observed increase in cell death, highlighting the cytotoxic effects of EMF exposure.

Discussion

Neurodegenerative Diseases:

  • Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) are characterized by the accumulation of amyloid plaques and Lewy bodies, respectively.
  • This study found that EMF exposure influenced the metabolism of APP and α-syn, proteins implicated in these diseases, suggesting a potential link to the pathogenesis of AD and PD.

Implications for EMF Exposure:

  • The findings suggest that even low-level EMF exposure can significantly alter protein metabolism associated with neurodegenerative diseases.
  • This study adds to the growing body of evidence indicating that EMF exposure might contribute to the development of conditions like AD and PD through mechanisms involving oxidative stress and protein aggregation.

Conclusion

The research conducted by Stefi et al. provides crucial insights into how EMF exposure affects key proteins involved in neurodegenerative diseases. By altering APP and α-syn metabolism, EMFs could potentially contribute to the development and progression of Alzheimer’s and Parkinson’s diseases. These findings underscore the need for further investigation into the molecular mechanisms underpinning these changes and highlight the importance of considering EMF exposure in public health discussions.

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